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Cited by 277Schizophrenia research and treatmentTreatment of Major DepressionMental Health and Psychiatry

Clozapine alone versus clozapine and risperidone with refractory schizophrenia

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Honer, William G., Thornton, Allen E., Chen, Eric Y.H., Chan, Raymond C.K., Wong, Jessica O.Y., Bergmann, Andrea, Falkai, Peter, Pomarol-Clotet, Edith +6 more·2006·New England Journal of Medicine
DOI 10.1056/nejmoa053222
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Abstract

BACKGROUND: The treatment of schizophrenia with multiple antipsychotic drugs is common, but the benefits and risks are not known. METHODS: In a randomized, double-blind study, we evaluated patients with schizophrenia and a poor response to treatment with clozapine. The patients continued to take clozapine and were randomly assigned to receive eight weeks of daily augmentation with 3 mg of risperidone or with placebo. This course of treatment was followed by an optional 18 weeks of augmentation with risperidone. The primary outcome was reduction in the total score for severity of symptoms on the Positive and Negative Syndrome Scale (PANSS). The secondary outcomes included cognitive functioning. RESULTS: A total of 68 patients were randomly assigned to treatment. In the double-blind phase, the mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups. There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment (P=0.38). The mean difference in the change in PANSS scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 (95 percent confidence interval, -7.3 to 7.0). The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P=0.02 for the comparison between the two groups in the change from baseline). The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter], P=0.04). The incidence and severity of other side effects did not differ between the two groups. CONCLUSIONS: In this short-term study, the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia. (ClinicalTrials.gov number, NCT00272584).

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  • In the Honer et al trial, there was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo on the PANSS.

    “• No statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo on the PANSS”

    From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [36]

  • In the Honer et al trial, the verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P = .02 for the comparison between the 2 groups in the change from baseline).

    “• The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P = .02 for the comparison between the 2 groups in the change from baseline).”

    From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [36]

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Research works printed but not linked: 3

  1. trolled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety. J Clin Psychiatry 2005;66:63- 72.
  2. Waddington JL, Youssef HA, Kinsella A. Antipsychotic polypharmacy and ab- sence of adjunctive anticholinergics over the course of a 10-year prospective study. Br J Psychiatry 1998;173:325-9.
  3. Chouinard G, Ross-Chouinard A, An- nable L, Jones BD. The Extrapyramidal Symptom Rating Scale. Can J Neurol Sci 1980;7:233.

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Authors
Honer, W. G., Thornton, A. E., Chen, E. Y. H., Chan, R. C. K., Wong, J. O. Y., Bergmann, A., Falkai, P., Pomarol-Clotet, E., McKenna, P. J., Stip, E., Williams, R., MacEwan, G. W., Wasan, K., & Procyshyn, R.
Affiliations
  • University of British Columbia (CA)
  • Simon Fraser University (CA)
  • University of Hong Kong (HK)
  • Sun Yat-sen University (CN)
  • Castle Peak Hospital (CN)
  • Saarland University (DE)
  • University of Cambridge (GB)
  • Riverview Hospital (CA)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2006-02-02
Volume
354
Issue
5
Pages
472-482
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa053222
OpenAlex
W1976741101
Cited by
277
References
39
Citations by year
2026: 5 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 24 · 2020: 6 · 2019: 12 · 2018: 10 · 2017: 11 · 2016: 11 · 2015: 11 · 2014: 12 · 2013: 14 · 2012: 18
FWCI
18.69
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords
refractory schizophrenia, clozapine, risperidone, antipsychotic augmentation, treatment-resistant schizophrenia, verbal working memory, fasting blood glucose, antipsychotic adverse effects
MeSH terms
Adult, Clozapine, Cognition, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Treatment Failure, Risperidone

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